Diagnostic imaging is an emerging technique in the field of medical equipment. For example, this technique is typically exploited for the assessment of blood perfusion, which finds use in several diagnostic applications and especially in ultrasound analysis. The perfusion assessment is based on the analysis of a sequence of ultrasound contrast images, obtainable by administering an ultrasound contrast agent (UCA) to a patient. The contrast agent acts as an efficient ultrasound reflector, so that it can be easily detected applying ultrasound waves and measuring a resulting echo-power signal. As the contrast agent flows at the same velocity as the blood in the subject, its tracking provides information about the perfusion of the blood in a body-part to be analyzed.
Suitable contrast agents include suspensions of gas bubbles in a liquid carrier. For this purpose, the gas bubbles are stabilized using emulsifiers, oils, thickeners or sugars, or by entraining or encapsulating the gas or a precursor thereof into a variety of systems. Stabilized gas bubbles are generally referred to as gas-filled microvesicles. The microvesicles include gas bubbles dispersed in an aqueous medium and bound at the gas/liquid interface by a very thin envelope involving a surfactant, i.e., an amphiphilic material (also known as microbubbles). Alternatively, the microvesicles include suspensions in which the gas bubbles are surrounded by a solid material envelope formed of natural or synthetic polymers (also known as microballoons or microcapsules). Another kind of ultrasound contrast agent includes suspensions of porous microparticles of polymers or other solids, which carry gas bubbles entrapped within the pores of the microparticles. Examples of suitable aqueous suspensions of microvesicles, in particular microbubbles and microballoons, and of the preparation thereof are described in EP-A-0458745, WO-A-91/15244, EP-A-0554213, WO-A-94/09829 and WO-A-95/16467, which are incorporated herein by reference.
The perfusion assessment process is typically implemented with the so-called destruction-replenishment technique. For this purpose, the body-part to be analyzed is first perfused with the contrast agent at a constant rate. The microbubbles are then destroyed by a flash of sufficient energy. Observation of the replenishment (or reperfusion) of the microbubbles in the body-part provides quantitative information about the local blood perfusion. For this purpose, the echo-power signal that is measured over time is fitted by a mathematical model, in order to extract quantitative indicators of blood perfusion; the information thus obtained can then be used to infer a physiological condition of the body-part. This technique has been proposed for the first time in Wei, K., Jayaweera, A. R., Firoozan, S., Linka, A., Skyba, D. M., and Kaul, S., “Quantification of Myocardial Blood Flow With Ultrasound-Induced Destruction of Microbubbles Administered as a Constant Venous Infusion,” Circulation, vol. 97 1998, which is incorporated herein by reference.
The mathematical models known in the art are generally based on the assumption that the contrast agent enters the body-part under analysis with a constant concentration during the reperfusion. For this purpose, the contrast agent must be provided as a continuous infusion. However, this requires an automatic infusion pump that provides a constant supply of the contrast agent through a catheter. Moreover, the continuous administration involves the use of a large amount of contrast agent. All of the above may increase the cost of the perfusion assessment process.
A different solution known in the art is that of administering the contrast agent as a bolus (i.e., a single dose provided over a short period of time, typically of the order of 2-20 seconds). In this case, the operation of providing the contrast agent is very simple, and it can be carried out by hand (for example, using a syringe); moreover, the bolus administration requires a small amount of contrast agent.
However, an inflow of the contrast agent in the body-part is not stationary in this case. Indeed, a typical bolus-type inflow shows a wash-in phase (in which the inflow increases over time following the bolus administration) and a wash-out phase (in which the inflow decreases after reaching its maximum value); moreover, the inflow of the contrast agent is generally different in a number of regions of the body-part at the same time. Therefore, in these conditions the mathematical models known in the art are not suitable for a rigorous representation of the perfusion process.
Attempts have been made to overcome the above-mentioned problem by administering the contrast agent as a “slow” bolus, over a period of time long enough to perform the replenishment analysis under a fairly constant infusion rate of the contrast agent. Nevertheless steady state conditions are not achievable because of the presence of the wash-out phase of the bolus, so that the accuracy of the results obtained is strongly limited.
The document “Quantification of perfusion of liver tissue and metastases using a multivessel model for replenishment kinetics of ultrasound contrast agents”, Martin Krix, Christian Plathow, Fabian Kiessling, Felix Herth, Andreas Karcher, Marco Essig, Harry Schmitteckert, Hans-Ulrich Kauczor, and Stefan Delorme, Ultrasound in Med. & Biol., Vol. 30, No. 10, pp. 1355-1363, 2004, which is incorporated herein by reference, proposes obtaining a whole perfusion curve by means of a further identical bolus administration. However, this requires additional operations on the patient that are time consuming. In any case, the accuracy of the results so obtained is very poor, due to the fact that it is difficult (if not impossible) to have two distinct bolus administrations that are really identical.